(59a) Advances in Intelligent Hydrogels for Biomedical Applications

Intelligent or smart polymers are polymeric materials that can respond to their surrounding environment, notable the physiological or biological environment, thus expanding or contracting at different rates. This type of response can be used either to construct biomedical devices, or to produce advanced responsive medical systems.

Among various types of polymers, hydrogels are the simplest carriers to be used as intelligent systems. These are three-dimensional, hydrophilic, polymeric networks able to imbibe large amounts of water or biological fluids. The networks are composed of homopolymers, copolymers or biohybrids and are insoluble in water due to the presence of chemical crosslinks (tie-points, junctions) or physical crosslinks such as entanglements or crystallites. These hydrogels exhibit thermodynamic compatibility with water that allows them to swell in aqueous media.

Hydrogels can be neutral or ionic based on the nature of the side groups. Depending on the physical structure of the networks they can be amorphous, semicrystalline, hydrogen-bonded structures, supermolecular structures and hydrocolloid aggregates. Hydrogels may also show swelling behavior dependent on the external environment. These polymers are physiologically responsive hydrogels where polymer complexes can be broken or the network can be swollen as a result of the changing external environment. They exhibit drastic changes in their swelling ratio especially as a function of pH, ionic strength, temperature and electromagnetic radiation

Random and graft copolymers, block copolymers and blends based on polymers such as poly(hydroxyethyl methacrylate), poly(N-isopropyl-2-acrylamide), poly(methacrylic acid) and poly(vinyl alcohol) will be discussed. Hydrogels are also used as carriers that can interact with the mucosa lining in gastrointestinal tract due to their ability to prolong their residence time at the delivery location. The interaction between such carriers and the glycoproteins in the mucosa is thought to occur primarily via hydrogen bonding. Therefore, materials containing a high density of carboxyl and hydroxyl groups appear to be promising for this type of application.

The idea of adhesion promoters diffusing across the polymer/mucin interface has also been introduced. Chains of polymerized ethylene glycol either freely loaded in the carrier or grafted to the polymer surface have been utilized as adhesion promoters. The ‘stealth’ properties of poly(ethylene glycol), have also been used to reduce the uptake of particulate carriers by the reticuloendothelial system. PEG has also been shown to both lengthen the biological half-life and reduce the immunogenicity of high molecular weight substances.

Biomimetic polymeric networks can be prepared by designing interactions between the building blocks of biocompatible networks and the desired specific ligands and by stabilizing these interactions by a three-dimensional structure. These structures are at the same time flexible enough to allow for diffusion of solvent and ligand into and out of the networks. These artificial materials can be used as unique systems or incorporated into existing drug delivery technologies that can aid in the delivery of biomolecules and restore the natural profiles of compounds in the body. In recent years, there has been considerable work in preparing materials and finding new uses for nanoscale structures based on biomaterials. Uses such as carriers for controlled and targeted drug delivery, micropatterned devices, systems for biological recognition, have shown the versatility of these biopolymeric materials.

We discuss large number of applications that have emerged in the past ten years and show how the hydrogel molecular structure affects the responsive behavior.